It has been shown that cocaine-seeking behavior in rats increases progressively over the first two months of withdrawal from cocaine self-administration. This time-dependent increase in drug seeking is termed "incubation" of cocaine craving. Exploring its underlying mechanisms may provide valuable insight into a disease, cocaine addiction, for which there is no effective treatment despite years of research. A protein cross-linking assay will be used, adapted for in vivo studies by our lab, to determine whether incubation of craving during withdrawal from cocaine self-administration is accompanied by changes in the trafficking of glutamate and dopamine receptors between the surface and intracellular compartments of nucleus accumbens (NAc) neurons. Our hypothesis, supported by preliminary data, is that incubation of drug-seeking is due in part to increased AMPA receptor surface expression, thus increasing the responsiveness of NAc neurons to glutamate inputs that trigger drug-seeking. Finally, activation of signaling pathways will be investigated as potential mechanisms for trafficking of AMPA receptors in rats that display time-dependent increases in cocaine-seeking behavior. [unreadable] [unreadable] [unreadable]